WORLD INTELLECTUAL PROPERTY ORGANIZATION
INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT)
(51) International Patent Classification 7 :
(11) International Publication Number: WO 00/67722
(43) Internationa] Publication Date: 16 November 2000 (16.11.00)
(21) International Application Number: PCT/USOO/11203
(22) Internationa] Filing Date: 26 April 2000 (26.04.00)
(30) Priority Data:
6 May 1999 (06.05.99)
(71) Applicant: COLOR ACCESS, INC. IUS/US]; 7 Corporate
Center Drive, Melville, NY 1 1747 (US).
(72) Inventors: MAMMONE, Thomas; 4 Spencer Street, Farming-
dale, NY 11735 (US). GAN, David, C; 50 Chichester
Street, Huntington Station, NY 11746 CUS).
(74) Agent: TSVEDOS, Estelle, L; Kenyon & Kenyon, One
Broadway, New York, NY 10004 (US).
(81) Designated States: AE, AG, AL, AM, AT, AU, AZ, BA, BB,
BG, BR, BY, CA, CH, CN, CR, CU, CZ, DE, DK, DM,
DZ, EE, ES, FI, GB, GD, GE, GH, GM, HR, HU, ID, BL,
IN, IS, JP, KE, KG, KP, KR, KZ, LC, LK, LR, LS, LT, LU,
LV, MA, MD, MG, MK, MN, MW, MX, NO, NZ, PL, PT,
RO, RU, SD, SE, SG, SI, SK, SL, TJ, TM, TR, TT, TZ,
UA, UG, UZ, VN, YU, ZA, ZW, AR1PO patent (GH, GM,
KE, LS, MW, SD, SL, SZ, TZ, UG, ZW), Eurasian patent
(AM, AZ, BY, KG, KZ, MD, RU, TJ, TM), European patent
(AT, BE, CH, CY, DE, DK, ES, FI, FR, GB, GR, IE, IT,
LU, MC, NL, PT, SE), OAPI patent (BF, BJ, CF, CG, a,
CM, GA, GN, GW, ML, MR, NE, SN, TD, TG).
With international search report.
Before the expiration of the time limit for amending the
claims and to be republished in the event of the receipt of
(54) Title: METHODS OF EXFOLIATION USING N-ACETYL GLUCOSAMINE
The present invention relates to a method of exfoliating and moisturizing the skin comprising the steps of topically applying a cosmetic
or pharmaceutical composition. The composition comprises an amino sugar, N-acetyl-D-glucosamine and related compounds.
FOR THE PURPOSES OF INFORMATION ONLY
Codes used to identify States party to the PCT on the front pages of pamphlets publishing international applications under the PCT.
Bosnia and Herzegovina
Republic of Moldova
The former Yugoslav
Republic of Macedonia
Trinidad and Tobago
United States of America
Central African Republic
Republic or* Korea
Republic of Korea
METHODS OF EXFOLIATION USING
Field of the Invention
5 The present invention relates to methods of substantially exfoliating the skin. In
particular, the invention relates to topically applied compositions containing an amino sugar in
the form of N-acetyl glucosamine.
Background of the Invention
1 0 This invention relates to methods of using N-acetyl glucosamine to exfoliate the skin. The
cells of the outermost layer of the stratum comeum are constantly shed naturally, by the normal
process of desquamation, as minute particles. When fully keratinised tissue loses its cellular
structure and reaches the surface of the stratum comeum, it breaks up into microscopic squames
and sheds off the surface of the skin. Microscopic squames at the skin surface are commonly
15 referred to as dead skin cells and make up a dead skin layer on the skin surface. The process of
desquamation has been estimated to cause a loss of tissue in an amount of up to 1 4 grams per day.
This loss is constantly replenished with cells from lower layers of the epidermis. Thus, the layers
of the epidermis are composed of cells moving up towards the surface in successive stages of
differentiation until death when they are finally sloughed off and lost to the environment.
2 0 Desquamation is one of the processes by which skin maintains its health and vitality as nutrients
and moisture are continuously replaced on the surface of the skin when dead skin cells are
removed. Normally, the desquamation process takes about 14 days (i.e., the corneocyte takes 1 4
days to reach the outermost layer of the strateum corneum to be shed). When desquamation does
not take place regularly, the surface of the skin tends to become rougher and more wrinkles and
25 other undesirable effects appear on the surface of the skin. However, in addition to or as an
alternative to the natural desquamation process, exfoliation is often used to rejuvenate and
enhance the health of the skin.
Exfoliation is a technique whereby dead skin cells are removed or sloughed from the skin
surface to promote a healthier and more youthful appearance to the skin. Several compounds are
3 0 known to be useful as exfoliants such as for example, alpha hydroxy acid ("AHA"), beta hydroxy
acid ("BHA'X retinoic acid ("retin A"), and enzymes. An exfoliant such as AHA breaks the bond
holding individual squames together and allows them to detach and shed.
Producing a variety of alternatives for exfoliation is desirable because skin types vary
among consumers and therefore, having a variety of exfoliants available to meet various
individual skincare needs of consumers is beneficial. Thus, there is a continued effort to find
additional alternative ways of aiding the sloughing ability of the skin and promoting its health for
5 various types of skin. This is, therefore, an object of the present invention.
Summary of the Invention
The present invention relates to a method for exfoliating the skin by topically applying
pharmaceutical or cosmetic compositions containing an exfol iating-effecti ve amount ofN-acety I-
1 0 D-glucosamine, N-acetylgalactosam ine, or a combination thereof. This method provides a natural
alternative to the exfoliation process that is as effective as other typical exfoliation techniques.
Detailed Description of the Invention
It has now been unexpectedly discovered that topically applied N-acetyl-D-glucosamine
15 or N-acetylgalactosamine containing compositions exfoliate the skin. Combinations of N-acetyl-
D-glucosamine and N-acetylgalactosamine can also be used. These compositions which exfoliate
the skin can also include chitin to enhance the process of exfoliation.
It is known that amino sugars are capable of modulating the adhesion of keratinocytes,
in vitro . It is disclosed by Brysk, M. in "Glycoproteins modulate adhesion in terminally
20 differentiated keratinocytes," that N-acetylglucosamine, N-acetylneuraminic acid and N-
acetylgalactosamine are involved in the dissociation of aggregates of glycoproteins that bind
corneocytes together. Specifically, amino sugars are known to inhibit the reaggregation of
corneocytes which have been dissociated into single squames by homogenization in ether.
Further, amino sugars in the form of N-acetylglucosamine have been used as an oral nutrient
2 5 supplement in conjunction with other topical cosmetic products, such as for example, products
offered by Life-Force, Inc. which include N-acetyl-D-glucosamine in the form of a pill taken as
a nutritional supplement. However, it is not suggested in the prior art to formulate a
pharmaceutical or cosmetic composition for topical application to the skin using N-
acetylglucosamine as an exfoliant. In fact, in W097/12597 it is disclosed that when studied to
3 0 determine its efficacy as a topical desquamating agent, N-acetyl-D-glucosamine was not found
to be effective. The exfoliant in W097/1 2597 is a compound comprising a chain of carbohydrates
linked by a linking moiety to an alkyl or alkenyl chain. Further, W097/12597, incorporated
herein by reference, only includes N-acetyl-D-glucosamine as one of the units forming the
carbohydrate portion which is linked by the linking moiety to the alkyl or alkenyl chain for
desquamation of the skin. It is not disclosed in W097/1 2597 that N-acetyl-D-glucosamine alone
can exfoliate the skin.
Compositions for topical application containing N-acetyl-D-glucosamine have been
5 disclosed for example, in JP 59013708, WO 98/52576, and U.S. Patent No. 5,866,142, each
incorporated herein by reference. To soften and moisturize the skin, a cosmetic containing an N-
acetyl amino sugar is disclosed in JP 59013708. A composition for alleviating itching and pain
containing N-acetyl-D-glucosamine is disclosed in W098/52576. In U.S. Patent No. 5,866,142,
a composition for exfoliating the skin has been disclosed, which includes N-acetyl-D-
1 0 glucosamine. The presence of N-acetyl-D-glucosamine contributes to enhancing the amount of
hyaluronic acid which the skin naturally produces in greater quantities in response to exfoliation,
induced by other compounds such as histidine. However, no exfoliating activity is attributed to
N-acetyl-D-glucosamine. A cosmetic composition containing N-acetylglucosamine and having
good adhesion to the skin (i.e., does not lift off of the skin) is disclosed in JP 81 88526. However,
15 the prior art does not disclose the ability of glucosamine, and particularly, N-acetyl-D-
glucosamine, to exfoliate the skin.
The composition of the present invention contains an exfoliating-effective amount of N-
acetyl-D-glucosamine, N-acetylgalactosamine, or a combination thereof. By the term
"exfoliating-effective amount" as used in the present specification, is meant an amount which is
20 effective to cause exfoliation of the skin. The amount of N-acetyl-D-glucosamine, N-
acetylgalactosamine, or a combination thereof, in the present invention will vary depending on
the desired strength or intensity of exfoliation. The N-acetyl-D-glucosamine or N-
acetylgalactosamine is present in the composition in an amount of about 0.01 to about 25.0
percent of the weight of the composition; preferably 0.5 to about 10.0 percent, and more
2 5 preferably about 1 .0 to 5.0 percent of the weight of the composition.
The N-acetyl-D-glucosamine or N-acetylgalactosamine per se is added directly to the
cosmetic or pharmaceutical composition by admixing; alternatively, extracts of materials
containing substantial quantities of N-acetylglucosamine or N-acetylgalactosamine as a
component can be used to provide the same concentration. These compositions can also contain
3 0 chitin. The amounts of chitin in the composition are also present in exfoliating-effective amounts
as previously described.
The intensity of exfoliation can also be controlled by the frequency with which the
compositions are applied to the skin and the compositions are applied periodically for a period
of time sufficient to exfoliate the skin. Accordingly, the compositions are applied to the skin for
a period of at least 2 months, and preferably for at least 4 months, during which time the
compositions are applied on a weekly basis. However, a preferred method of obtaining the
benefits of the composition is via chronic topical application of the composition to exfoliate the
5 skin. It is suggested, as an example, that "chronic" application be within a range of from about
once per week to about 4 to 5 times weekly, preferably daily, most preferably twice daily. By
"chronic" application, it is meant herein that the period of topical application may be over the
lifetime of the user, preferably for a period of at least about 6 months to about 20 years, more
preferably from about 1 year to about 10 years, and still more preferably from about 2 years to
10 about 5 years, thereby resulting in regular desquamation, which may aid in reducing the
appearance of fine lines and wrinkles due to chronological aging or photoaging.
The method of the present invention may include applying in addition to the exfoliating
effective amount of N-acetyl-D-glucosamine or N-acetylgalactosamine, other optional
components, depending on the intended end use of the compositions. These include, but are not
15 limited to, additional exfoliants, preservatives, fragrances, emollients, antiseptics,
antiinflammatories, antibacterials, stabilizers, antioxidants, vitamins, pigments, dyes, humectants,
and propellants, as well as other classes of materials the presence of which in the compositions
may be cosmetically, medicinally, or otherwise desired. Such components can be found in the
CTFA International Cosmetics Ingredients Dictionary. Examples of additional exfoliants include
20 but are not limited to chemical exfoliants such as AHAs, for example, lactic acid, or BHAs, for
example, salicylic acid, or physical exfoliants such as pumice, polyethylene, walnut shell powder,
and the like, or combinations thereof. The amount of additional exfoliants alone or in
combination will depend on the type of exfoliant and the strength of exfoliation desired.
Preservatives employed, may be in an amount of from about 0.01 to about 2.00 percent,
25 preferably from about 0.02 to about 1 .00 percent, of the formula weight. Examples of suitable
preservatives are BHA, BHT, propyl paraben, butyl paraben or methyl paraben or an isomer,
homolog, analog or derivative thereof.
For topical application, according to the method of the present invention, the
compositions can also be formulated with a variety of cosmetically and/or pharmaceutical ly
30 acceptable vehicles. Accordingly, the compositions of the present invention comprise a
pharmaceutical^ or cosmetically acceptable carrier, in an amount appropriate to accommodate
the other components of the formulation. The term "pharmaceutical ly and/or cosmetically
acceptable vehicle" refers to a base, for either pharmaceutical or cosmetic use, within which N-
acetyl-D-glucosamine or N-acetylgalactosamine is soluble and which will not cause harm to
humans or other recipients. As used herein, "pharmaceutical" or "cosmetic" will be understood
to encompass both human and animal pharmaceuticals or cosmetics. There are few limitations
on the type of base which is suitable for the compositions containing N-acetyl-D-glucosamine or
5 N-acetylgalactosamine. The vehicle may be aqueous, nonaqueous or a combination thereof
appropriate for the formulation desired.
The compositions can be prepared in any form convenient for topical application to the skin.
Such forms include, but are not limited to gels, creams, dispersions, emulsions (water-in-oil or oil-
in-water), suspensions, creams, lotions, gels, foams, mousses and the like. In a preferred
1 0 embodiment, the carrier is a suspension, dispersion or emulsion. The emulsion may be an oil-in-
water emulsion, or a water-in-oil emulsion. These emulsions contain one or more oil components,
an aqueous component, and a specific emulsifier component chosen depending on the nature of
the desired emulsion.
The invention is further illustrated by the following non-limiting examples.
A composition, according to the present invention is prepared as follows:
To prepare the composition, the materials are combined in the order above by mixing.
2 0 The composition is topically applied to the skin for exfoliation.
A composition, according to the present invention is prepared as follows:
25 To prepare the composition, the materials are combined in the order above by mixing.
The composition is topically applied to the skin for exfoliation.
A composition according to the present invention, containing IM-acetyl-D-glucosamine,
30 is studied to determine the effect on desquamation. A panel of individuals is selected to
participate in the test The selected participants are IS females between ages 21 and 65 years.
Participants are given the composition to take home and self administer on their right hand two
times a day, once in the morning after washing and once in the evening at least 1 5 minutes before
bedtime for 4 weeks. The left hand is the untreated control sample. Participants are allowed to
use only the composition being studied and are to log its use in a daily diary. At intervals of 2 and
4 weeks, the participants return for testing without applying the composition for at least 1 2 hours.
The participants are tested without moisturizer or any other product on the skin of their hands.
5 Their skin is acclimated to an environment of about 70° F, and about 40 percent relative humidity
for about 20 minutes.
Skin exfoliation is measured with D-Squame discs and image analysis. Specifically, the
amount of flakes removed from the skin surface using D-Squame discs are measured. Firmly and
evenly, 4 D-Squame discs are pressed on the back of each hand using a hand held uniform
10 pressure device. The discs are removed by gently pulling them away from the skin. After
removal, the discs are mounted on clear microscope slides and evaluated with an image analyzer,
OPTIMA. A camera takes a picture of the slide and the average gray value is measured to
determine the corresponding density of stratum corneocytes. Denser samples have higher gray
15 Results show that the composition reduces skin flakiness after 2 weeks and 4 weeks of
treatment when compared to untreated control hand area. After 2 weeks there is about a 15.8
percent decrease and after 4 weeks there was about 1 63 percent decrease in skin flakiness,
thereby showing its utility in desquamation.
What we claim is:
1 . A method for exfoliation of the skin comprising applying to the skin a composition
comprising an exfoliating-effective amount of an amino sugar selected from the group
consisting of N-acetyl-D-glucosamine, N-acetylgalactosamine, and a combination thereof.
2. The method according to claim 1 wherein the amino sugar is present in an amount
from about 0.01 percent to about 25.0 percent of the weight of the composition.
3. The method according to claim 2 wherein the amino sugar is present in an amount
from about 0.5 percent to about 10.0 percent of the weight of the composition.
4. The method according to claim 3 wherein the amino sugar is present in an amount
from about 1 .0 percent to about 5.0 percent of the weight of the composition.
5. The method according to claim 1 wherein the composition is applied to the skin for
a period of at least 4 months.
6. The method according to claim 5 wherein the composition is applied weekly.
7. The method according to claim 1 wherein the composition is applied to the skin for
a period of at least 2 months.
8. The method according to claim 1 wherein the compositions are applied from about
4 to about 5 times a week.
9 The method according to claim 8 wherein the composition is applied two times a day.
1 0. The method according to claim 1 wherein the composition further comprises chitin.
INTERNATIONAL SEARCH REPORT
Men nal Application No
A. CLASSIFICATION OF SUBJECT HATTER
IPC 7 A61K7/48
According to International Patent Classification (IPC) or to both national classification and IPC
a FIELDS SEARCHED
Nfcnimum documentation searched (classification system followed by classification symbols)
IPC 7 A61K
Documentation searched other than minimum documentation to the extent that such documents are included in the fields searched
Electronic data base consulted during the international search (name of data base and. where practical, search terms used)
EPO-Internal , CHEM ABS Data
C. DOCUMENTS CONSIDERED TO BE RELEVANT
Category 0 Citation of document, with indication, where appropriate, of the relevant passages
Relevant to claim No.
EP 0 852 946 A (PAOLI AMBROSI GIANFRANCO
DE) 15 July 1998 (1998-07-15)
page 4, line 37
page 10, line 14 - line 18
WO 97 12597 A (L 'OREAL)
10 April 1997 (1997-04-10)
cited in the application
the whole document
Further documents are listed in the continuation of box C.
Patent family members are listed in annex.
° Special categories of cited documents :
"A" document defining the general state of the art which is not
considered to be of particular relevance
*E* earlier document but published on or after the international
V document which may throw doubts on priority daimfs) or
which is cited to establish the publication date of another
citation or other special reason (as specified)
*0" document referring to an oral disclosure, use, exhibition or
"P* document published prior to the international filing date but
later than the priority date claimed
T* later document published after the international filing date
or priority date and not in conflict with the application but
cited to understand the prtrtctpie or theory underlying the
"X" document of particular relevance; the claimed invention
cannot be considered novel or cannot be considered to
involve an inventive step when the document is taken alone
*Y" document of particular relevance; the claimed invention
cannot be considered to involve an inventive step when the
document is combined with one or more other such docu-
ments, such combination being obvious to a person skilled
in the art
"V document member of the same patent family
Date of the actual completion of the international search
28 August 2000
Date of mailing of the international search report
Name and mailing address of the ISA
European Patent Office, P.B. 581 8 Patentlaan 2
Tel. (401-70) 340-2040, Tx. 31 651 eporf.
Pel 1 i Uablat, B
Form PCT/ISAOIO (second shaet) (July 1992)
INTERNATIONAL SEARCH REPORT
Biffonnatlon on patent family members
cited in search report
Form PCT/ISA/210 (pitont tardy annex) (Jtfy 19821